Dysplasia and carcinoma of the conjunctiva comprise a spectrum of atypical proliferations of the conjunctival mucosa. The pathogenesis of these lesions has not been determined. Human papillomavirus (HPV) is now epidemic as a sexually transmitted disease. Certain genotypes of HPV have been implicated as possible causative agents in the development of proliferative squamous lesions of the uterine cervix, vulva, anus, larynx, and tongue. While HPV antigens and HPV DNA are demonstratable in benign papillomas of the conjunctiva, uncertainly persists as to the role of HPV in more malignant squamous lesions of the conjunctiva. The polymerase chain reaction (PCR) is a recently developed technique in which target DNA sequences are amplified in vitro to levels that greatly enhance their detection using conventional dot blot hybridization techniques. We have applied this technique to dysplastic and neoplastic lesions of the conjunctiva. 12 of 16 (75%) specimens examined provided evidence for the presence of HPV type 16-related DNA sequences. We propose to use PCR and Southern analysis to determine whether HPV plays a role in the development of conjunctival dysplasias and carcinomas. The studies are prompted in part by the increasing reservoir of HPV in the general population, and the potential of HPV to involve the eye in greater numbers of patients at some time in the future.